Water → 3,5-dichloro-N-(4-fluorobenzyl)-N-(3-((4-fluorobenzylamino)methyl)benzyl)-2-hydroxybenzamide

HRID 1889652Notes

Reaction equation

HRID 1889652 reaction equation
[Cl:1][C:2]1[C:3]([OH:12])=[C:4]([CH:8]=[C:9]([Cl:11])[CH:10]=1)[C:5]([OH:7])=O.CCN=C=NCCCN(C)C.Cl.[C:25]1([CH2:41][NH:42][CH2:43][C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][NH:32][CH2:33][C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[CH:26]=1.O>CN(C=O)C.C1C=CC2N(O)N=NC=2C=1>[Cl:1][C:2]1[C:3]([OH:12])=[C:4]([CH:8]=[C:9]([Cl:11])[CH:10]=1)[C:5]([N:32]([CH2:33][C:34]1[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=1)[CH2:31][C:27]1[CH:28]=[CH:29][CH:30]=[C:25]([CH2:41][NH:42][CH2:43][C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)[CH:26]=1)=[O:7]

Participants

7

Reactant 4

HCID 962WaterHCID 94453,5-Dichlorosalicylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66616478(4-Fluoro-benzyl)-{3-[(4-fluoro-benzylamino)-methyl]-benzyl}-amine

Product 1

HCID 666164993,5-dichloro-N-(4-fluorobenzyl)-N-(3-((4-fluorobenzylamino)methyl)benzyl)-2-hydroxybenzamideYield 21.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 757711-HydroxybenzotriazoleSolvent

Procedure

To a solution of 3,5-dichloro-2-hydroxybenzoic acid (300 mg, 1.449 mmol) in DMF (5 mL) at rt was added EDCI.HCl (300 mg, 1.565 mmol) followed by N,N′-(1,3-phenylenebis(methylene))bis(1-(4-fluorophenyl)methanamine) (365 mg, 1.036 mmol) in 2 mL of DMF and hydrated HOBt.H2O (200 mg), and the reaction mixture was stirred at rt overnight. The mixture was directly purified by prep HPLC to provide a monoacylated product 3,5-dichloro-N-(4-fluorobenzyl)-N-(3-((4-fluorobenzylamino)methyl)benzyl)-2-hydroxybenzamide (0.12 g, 21.4%) and a diacylated product, N,N′-(1,3-phenylenebis(methylene))bis(3,5-dichloro-N-(4-fluorobenzyl)-2-hydroxybenzamide) (0.245 g, 32.4%). 1H NMR (CD3OD): δ 7.34˜6.80 (m, 16H), 4.59 (s, 4H), 4.24 (s, 4H); MS (ESI): (M+H)+=731.

Workup

  1. customThe mixture was directly purified by prep HPLC

Sources & evidence

ORD record
ord-248c6a1ea86c4112981d45c9970965f6
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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